DESCRIPTION: The aim of this proposal is to determine the relation of hostility to biological processes implicated in atherogenesis. At this time, pathophysiological mechanisms underlying the hostility-coronary heart disease (CHD) link are incompletely defined. It is believed that excessive and prolonged sympathetic nervous system (SNS) activation to stressors is one such mechanism. Hostile persons respond to psychologically challenging situations with excessive and prolonged cardiovascular (CV) and neuroendocrine (NE) responses, which are positively associated with lipid levels. Hostile men also show reduced beta-adrenergic receptor (AR) number of lymphocytes and reduced beta-AR responsiveness to isoproterenol (iso) stimulation. In light of this evidence the investigators hypothesize that high hostile persons stress-induced CV and NE hyperreactivity are associated with reduced beta(2)-AR number and iso-stimulated cAMP. The investigators also propose to examine the association between hostility and pro-inflammatory cytokines and adhesion molecules on circulating monocytes. The monocyte-macrophage has been implicated in the earliest stages of atherosclerosis with morphologic observations showing the adherence of monocytes to the vascular endothelium. They hypothesize that hostility is associated with stress-induced increases in the expression of cytokines and adhesion molecules on monocytes. In line with this hypothesis, they have recently shown that the arousal of negative affects, specifically anger/irritation and anxiety, is associated with stress-induced increases in monocyte-derived interleukin-1 beta in high hostile persons. Toward critically testing these hypotheses, the investigators propose the following specific aims: 1) to determine if high hostiles' exaggerated CV and NE responses are associated with a reduced beta-AR number and iso-stimulated cAMP; 2) to determine if individuals who are high hostile and have reduced beta(2)-AR number and iso-stimulated cAMP, and thus the most physiologically reactive to stressors, show significantly higher lipid levels; 3) to determine if in high hostile, arousal of negative affects is associated with stress-induced increases in the expression of monocyte-derived cytokines and adhesion molecules; and 4) to determine if in high hostile, SNS outflow, as assessed by acute laboratory catecholamine responses or chronic effects on beta(2)-AR number, and lipids are positively associated with stress-induced changes in monocyte markers. If the hypotheses are confirmed, it will identify molecular-cellular markers of increased CHD risk in hostile persons.